The present invention is concerned with a liquid analysis apparatus and, more particularly, holding and positioning an analysis insert element on a rotor thereof.
A centrifugal analysis apparatus is known from Federal Republic of Germany Patent Specification No. 30 44 385. It is used for clinical chemical analysis, especially of components of blood and serum, as a basis for medical diagnosis. The liquid sample to be measured is introduced into the insert element and, by centrifuging, mixed with reagent contained in the insert element. Besides the optical measurement chamber, the insert element can contain several mixing chambers which are connected together in such a manner that the liquid can flow over between the individual chambers in the case of appropriate control of the rotor movement. Thus, by control of the rotor movement, the mixing with reagents, the incubation and the course of the reaction can be controlled. The reagents can, for example, be dry reagents introduced into the insert elements by the manufacturer. However, liquid reagents can also be used. With the help of such an analysis apparatus of the rotor type, several liquid samples can be investigated simultaneously, which considerably reduces the time needed for the analysis. In the case of the known centrifugal analysis apparatus, the rotor is constructed as a flat, circular disc upon which the insert elements can be fixed around the axis of rotation at an angle to each other.
A photometer which is especially useful for a centrifugal analyser of the above type is known from Federal Republic of Germany Patent Specification No. 29 30 431. This is a polychromic photometer which permits the measurement of the parameters of a plurality of samples on a rotor in a particularly short time and at several selectable light wavelengths.
From U.S. Patent Specification No. 3,713,775, there is known a centrifugal analysis apparatus in the case of which several insert elements provided with the sample liquid to be measured are assembled together by means of a flexible carrying body to give a unit. The carrying body, bent round the axis of rotation of the rotor, is fixed on to the rotor, the insert elements running radially to the axis of rotation of the rotor. The carrying body fixes and positions the insert elements relative to the beam path of the photometer. The carrying element is placed from above radially on the rotor.
Another centrifugal analysis apparatus is known from U.S. Patent Specification No. 4,135,883. In the case of this analysis apparatus, the rotor has, axially to its axis of rotation, pockets which are accessible from above, into which pockets the insert elements can be inserted and clamped.
In the case of the known analysis apparatus, only relatively few insert elements can be simultaneously fixed to the rotor. The transillumination surface of the measurement chamber is comparatively large in order to provide substantially constant measurement conditions of the photometer, even in the case of low requirements for positioning exactitude. Furthermore, in the case of the known analysis apparatus, the insert elements are placed radially from above on to the rotor. During operation, the insert elements are freely subjected to the ventilator action of the rotor and are uncontrollably cooled by the air flow produced. Insofar as the rotor rotates in a fixed-positioned housing and is to be maintained by means of a heating device at a predetermined temperature level, only relatively wide temperature limits can be maintained since, for the insertion of the insert elements, a large housing opening is necessary.
It is an object of the present invention to provide an analysis apparatus for the photometric determination of a parameter of a liquid, especially a centrifugal analysis apparatus, in the case of which the opening section of the rotor necessary for the insertion of the insert elements is as small as possible in order to simplify the maintaining constant of the rotor temperature. Furthermore, the holding of the insert elements is to be constructed in such a manner that an automatic insertion of the insert elements is also to be possible with only a small constructional expense. In addition, the rotor is to be capable of simultaneously accommodating and exactly positioning a large number of insert elements.
According to the present invention, this object is achieved in that the holding means are constructed as guiding chambers which are radial to the axis of rotation of the rotor and outwardly open peripherally. The insert elements, each having an elongated body with the optical measurement chamber near one end of the elongated body and a positioning trough on one side of the elongated body, can be respectively inserted into the guiding chambers substantially radially to the axis of rotation of the rotor with the positioning trough of each insert element on a lateral side thereof and adjacent the outer periphery of the rotor. Positioning and holding means on the rotor position the optical measurement chamber of each insert element in its respective guiding chamber at a position adjacent the outer periphery of the rotor and hold the insert element therein during the rotation of the rotor. For this, the positioning and holding means has a fixed element in a fixed position relative to the rotor on a lateral side of each guiding chamber at a position adjacent the outer periphery of the rotor and facing the positioning trough of the insert element circumferentially spaced therefrom when the insert element is initially received in its respective guiding chamber in a first position therein, and adjustment means. The adjustment means move the received insert element circumferentially into a second position engaging said fixed element with the positioning trough thereof, whereby said positioning trough and said fixed element are in a locking configuration in said second position.
The insert elements are inserted radially into the rotor from the outside through an opening with a relatively small cross-section, the rotor preferably being located in an insert element exchange position by means of a substantially radially movable locking means. The insertion can take place by a relatively simple automatic insertion device. The positioning and holding means not only locate the insert element in the guiding chamber but also align the measurement chamber exactly to the optical beam path of the photometric measurement apparatus. The exact alignment is necessary since the transillumination cross-section of the measurement chamber is very small because of its small volume. The analysis device according to the present invention fulfils relatively high tolerance requirements. In the case of a rotor diameter of 320 mm. and a speed of rotation of 3000 r.p.m., radial and tangential tolerances of the measurement chamber relative to the optical beam path of the photometric measurement apparatus of, for example, 50 .mu.m. can be maintained.
The positioning and holding means alternatively could be a trough provided in the wall of the guiding chamber, a lug or rib formed on to the insert element engaging flatly into this trough. Since the production of such a positioning trough can involve difficulties, the preferred positioning and holding means is formed as a pin projecting parallel to the axis of rotation of a rotor and the positioning trough is on the insert element.
The pin preferably passes completely through the base disc of the rotor and emerges again on the side of the base disc axially remote from the holding means. The emerging end of the one-piece pin forms a guide pin for a control light barrier of the photometer. In this way, the measurement tolerances between the guide pin and the measurement chamber of the positioned insert element are further reduced.
The guiding chambers are preferably almost completely closed by walls on the rotor and/or by walls on the frame of the apparatus arranged at a small distance from the rotor and parallel to its outer surfaces. The convection cooling of the insert elements in the case of rotation of the rotor and the evaporation of the contents of the insert elements is, therefore, comparatively small. The guide chambers can hereby be utilised as air-conducting canals which bring tempered air from a temperature-regulating air source into close heat-exchange contact with the insert elements, which improves the time constancy of the regulation.
In a first preferred embodiment, an adjustment means is provided on the rotor as a tiltably mounted lever, which acts as a positioning element, and is pre-stressed by a spring against the insert element in the direction towards the positioning and holding means. Instead of or also in addition to the spring, for the production of the prestressing there can also be used a fly-weight which becomes effective when the rotor is rotating. The lever presses the positioning means for the insert element against the complementary positioning and holding means, whereby the measurement chamber of the insert element, which is preferably closely adjacent to the positioning means becomes aligned relative to the rotor and its indexing means controlling the photometric measurement apparatus and is simultaneously located.
On the apparatus frame, there can be provided a movable lock as locking means which, when the rotor is stationary in a pre-determined insert element exchange position, can be moved into the tilt path of the lever. The locking means non-rotatably locks the rotor, standing in the insert element exchange position, on the apparatus frame so that this cannot rotate during the exchange of the insert elements. On the locking means, there is provided an impingement face facing counter to the insertion movement of the locking means, which co-operates with a stop face on the lever. The stop face is so constructed that, in the case of an insert element being inserted into the guiding chamber but incorrectly positioned, it prevents the pulling out of the locking means and thus the operation of the apparatus. The throwing out of non-located insert elements during the centrifugal operation is thus prevented with certainty.
The locking means preferably forms a constructional unit with an ejector which brings the positioning means of the insert element and of the positioning and holding means out of engagement when the locking means is present in the tilting path of the lever and thus moves them apart counter to the direction of prestressing of the lever in the circumferential direction of the rotor. Because of its stopping function, the locking means can only be moved back after removal of the ejected insert element from the rotor.
In a second preferred embodiment, the adjustment means has a spring engaging between the positioning element and the rotor, which spring forcefully presses the positioning element, movable in the circumferential direction of the rotor, against the rotor-fixed part of the contact face of the positioning organ of the holding means. This rotor-fixed part of the positioning and holding means can be a side wall of the guiding chamber. In this embodiment, the opening cross-section of the guiding chamber is particularly small. For the tempering of the insert element by air flowing along it, an essentially close contact can be maintained over the whole length of the insert element, which facilitates the maintenance of a desired temperature.
In the stress path between the spring and the positioning element, there is preferably provided a pressure piece slidably guided on the rotor. By means of an operational part movably guided on the apparatus frame, which part can, when the rotor is stationary, be moved into the path of movement of the pressure piece, on the one hand the rotor can be locked and, on the other hand, the pressure piece can be lifted up, counter to the force of the spring, from the positioning element. A thrust surface on the operational part moves the positioning element out of its engagement position positioning the insert element. The spring force is hereby taken up from the operational part directly and not via the positioning element, which increases the life of the positioning element.
The pressure piece is mounted substantially radially movably on the rotor and has a wedge-shaped sliding surface directed radially outwardly obliquely to the circumferential direction, which sliding surface, by the action of the force of the spring, pushes the positioning element to the insert element. For the accommodation of the spring, formed, for example as a helical pressure spring, there is a relatively large amount of space available in the radial direction towards the rotor. Consequently, the spring can be strongly dimensioned so that the insert element itself can then be surely pressed on its contact faces if, because of constructional inexactitudes, it should be bent. The pressing-on force can be further increased by an appropriate choice of the engagement angle of the wedge-shaped sliding surface.
In the case of this embodiment, too, for the reduction of the positioning tolerances, the control pin of a control light barrier is not applied to a base disc of the rotor but on the positioning element. The control pin projects through an opening of the base disc.
A further reduction of the positioning tolerances is obtained when the stop trough and the measurement chamber are closely adajacent. Finally, for the further reduction of the positioning tolerances in the case of insert elements constructed as synthetic resin formed parts, the stop trough and the greater part of the inner wall of the measurement chamber are shaped by the shaped surface of a common, one-piece shaping tool part of an injection moulding apparatus.
The analysis apparatus can, without problems, be automatically loaded with insert elements. In a constructively simple embodiment, on the apparatus frame there is movably provided at least one magazine which has a plurality of recesses for insert elements open towards the rotor. The magazine can be a drum with axis-parallel recesses distributed on the circumferential mantle or a disc with radially-running, trough-shaped recesses staggered in the circumferential direction. Especially simple magazines have a tray shape and carry the insert elements in recesses which are parallel to one another and are especially trough-shaped. A transport device co-ordinates the recesses successively to the insert path of the guiding chambers of the rotor which are stationary in a predetermined insert element exchange position and pushes the insert elements out of the magazine into the guiding chambers or from the guiding chambers into the magazine.
For this purpose, the transport device can have a slide movably mounted radially to the axis of rotation of the rotor, the slide having gripping means for gripping the insert elements. The recesses of the magazine, the guiding chambers and guiding surfaces extending along the slide guide form a substantially continuous, straight-lined guiding canal in which the insert elements lie movably. Therefore, the gripping means must not be immovably coupled with the insert elements. It suffices when it can push or draw the insert elements along the guide canal. The gripping means can be constructed as a simple carrier movably held on the slider.
In order not to have to apply an electrical drive on the slider for the movement of the gripping means, and consequently to avoid having electrical leads following the slider movement, it is preferably provided that the transport device has, on the apparatus frame, a cam rod rotatably mounted about an axis parallel to the slider guide, along which the gripping means slides in the case of movement of the slider. The cam rod is rotated by a motor fixed on the apparatus frame or the like and, in a first rotational position, brings the gripping means into engagement with the insert element and, in a second rotational position, out of engagement.
The insert elements are preferably provided with a magnetic data carrier layer on one of their surfaces which, seen laterally, are in the direction of movement. On the data carrier layer there can be stored characterising data of the liquid sample to be measured, as well as programme data concerning the specific chronological rotation programme for the insert element used. By means of a magnet head, the data can be read off upon conveying the insert element to the magazine or to the rotor and can possibly be supplemented by result data or the like.
The transducer slot of the magnet head must, over its whole length, lie against the data carrier layer of the insert element. For this purpose, the magnet head and/or a guide part for the insert element associated therewith must be movably mounted. In a preferred embodiment, the guide part has two guiding surfaces which are parallel in the direction of movement of the insert elements and, away from the magnet head, are inclined towards one another, for the edge guiding of adjacent, parallel longitudinal edges of the insert element. In this way, the insert element can tilt about its longitudinal axis and lie against the magnet head. In addition, the magnet head is preferably suspended cardanically, for example, on a leaf spring running substantially parallel to the data carrier layer.
For sufficiently exact measurement results, the reactions in the insert elements must be carried out at a constant, predetermined temperature of, for example, 37.degree. C..+-.0.1.degree. C. The maintaining constant of the temperature takes place extraordinarily well when the inner chamber of the rotor receiving the insert elements is substantially closed and can be supplied via a central opening of the rotor with air from a source of air temperature controlled by means of a first control circuit. As already mentioned, the inner chamber of the rotor can hereby be closed off by non-rotating walls or by walls fixed to the housing. In particular, the guiding chambers are so constructed that they form radial air conducting canals along the insert elements and essentially completely enclose the insert elements. The air eddying in the case of rotation of the rotor has, in this way, only a very small influence on the temperature in the region of the insert elements. The tempered air introduced via the central opening is substantially utilised for the tempering of the insert elements.
The special air introduction in the rotor region has, as a result, an especially short time constant for the temperature regulation. This can thereby be advantageously utilised in that, during the loading procedure of the insert elements, the air introduction is completely switched off, in order to reduce evaporation phenomena. It suffices again to switch on the air introduction shortly before the measurement. Furthermore, even with a single regulating circuit, this type of air introduction permits the temperature to be adjusted sufficiently constantly in the region of the rotor. However, for the further improvement of the temperature regulating properties, the rotor can additionally be arranged in a substantially closed housing forming or enclosing the apparatus frame, the inner air temperature of the housing being capable of temperature regulation via a heating device by means of a second regulating circuit. A control controlling the rotation of the rotor can, in the case of centrifugal operation, possibly change the desired temperature value of the first regulating circuit a predetermined period of time before commencement of the centrifugal operation by a predetermined temperture value. Thus, for example, it can decrease the temperature in order to counter the temperature change due to surrounding air being sucked into the housing by the rotation.
For the measurement of the actual temperature at the place of the insert elements, it is preferable to provide in one of the guiding chambers of the rotor a temperature sensing device in a housing corresponding to the shape of the insert element. The signals corresponding to the measured temperature can be transmitted via optocouplers or via sliding rings or the like to the control and possibly to the regulating circuits.
It is to be stressed that the above-explained temperature control can also be employed in the case of other forms of analysis apparatus.
A further aspect of the present invention, which can also be employed in the case of analysis apparatus other than the above explained apparatus, provides a way of reducing the imbalance of the rotor in a simple manner in the case of partial loading, especially when the total number of the insert elements to be loaded is not fixed before the loading. For this purpose, the loading operation of the rotor can be controlled by a control which, after loading of a predetermined number of adjacent guiding chambers of the rotor with insert elements in a constant rotational loading direction, alternatingly there is loaded either a predetermined number of adjacent guiding chambers lying essentially diametrically opposite to the last supplied of the guiding chambers or there is loaded a predetermined number of again adjacent guiding chambers with insert elements adjacent the last supplied holding means. The predetermined number corresponds to the number of insert elements producing the maximum permissible imbalance. Since the rotor does not have to be rotated through about 180.degree. after each loading step but rather, in each case, alternatingly adjacent and diametrically opposite lying guiding chambers are loaded, the loading and unloading time of the rotor can be kept relatively short in spite of the balancing of the imbalance. In order to keep the imbalance as small as possible, after the loading in each case of a single guiding chamber, subsequently the approximately diametrically opposite-lying guiding chamber and the immediately adjacent guiding chamber in the rotational loading direction is, in each case, loaded with an insert element. The unloading of the rotor can take place correspondingly.
According to another aspect of the present invention, which can also be used in the case of analysis apparatus other than according to the present invention, for the avoidance of imbalance phenomena in the case of loading and unloading of the rotor, the rotor carries, for each guiding means, a flyweight movable radially between an inner and an outer position, the insert element inserted into the guiding chamber locating the flyweight of its guiding chamber in the inner position. The inner position, the outer position, as well as the weight of the flyweight and of the insert element are so coordinated with one another that the flyweight in the outer position produces essentially the same centrifugal force as the flyweight located in the inner position by the insert element and the insert element together. In the case of radially insertable insert elements, the flyweight is preferably radially displaceable on the rotor and, in the case of the insertion of the insert element, is taken along by this form the outer position into the inner position. The flyweight is preferably a component of the regulating means, for example an arm of the above-mentioned lever or the pressure piece.